Apparatus and method for testing integrity of an ultrafilter membrane

ABSTRACT

An apparatus for an extracorporeal treatment of blood has a supply line, a waste line, and an ultrafilter inserted in the supply line. An air inlet line is connected to a first chamber of the ultrafilter. A pressure sensor is configured for detecting pressure in the waste line or a second chamber of the ultrafilter. A controller is configured to perform an integrity test procedure for detecting when an ultrafilter membrane of the ultrafilter has multiple or single fiber breaks. A method of testing the ultrafilter is also disclosed.

PRIORITY CLAIM

The present application is a continuation of U.S. Application No.17/050,050, filed Oct. 23, 2020, which is a National Phase ofInternational Application No. PCT/EP2019/060246, filed Apr. 19, 2019,which claims priority to EP Application No. 18169176.7, filed Apr. 25,2018. The entire contents of each application are incorporated herein byreference and relied upon.

DESCRIPTION

The invention relates to an apparatus and to a method for testing theintegrity of the semipermeable membrane of one or more ultrafilters. Theinvention may apply for testing the membrane integrity of one or moreultrafilters in apparatus for extracorporeal blood treatment. Forexample, the hydraulic circuit of apparatus for hemodialysis, orhemofiltration, or hemodiafiltration may include one or moreultrafilters configured for removing germs and other undesired particleswhich may be present in the dialysis liquid and/or in the replacementliquid prepared by the apparatus. As ultrafilters are typically used fora number of treatments, the ultrafilters membrane integrity needs to beperiodically verified in order to guarantee the membrane ability topurify liquid.

Various methods have been used in the past to check the integrity of anultrafilter membrane. In particular, the testing methods used in morerecent years have strived to be reliable in the detection of ruptures ofthe membrane, without requiring excessive complication on the apparatusand using as possible components already present in conventionalextracorporeal blood treatment apparatus.

For example, EP 1897605 B1 relates to a method and apparatus for testingintegrity of an ultrafilter membrane wherein gas is fed into a chamberof the tested ultrafilter via a feed line. Gas is put under pressure bya given amount of liquid also fed through the same feed line. Then, ameasure of liquid flow is made to detect leakage through the ultrafiltermembrane.

WO 2012124425 A1 relates to a hemodialysis apparatus wherein the controlsystem is configured for executing a method of testing the integrity ofan ultrafilter membrane by filling a part of the hydraulic circuit withair, creating a negative pressure in the water filled part of thehydraulic circuit, and monitoring the negative pressure thus created.

In particular, the control system operates the dialysis pump to create afirst negative pressure on the liquid side of the tested ultrafilter,then stops the dialysis pump and operates an ultrafiltration pump tocreate a second and more negative pressure. The control system thenverifies that the second more negative pressure remains substantiallystable. If this does not happen a defective membrane is identified.

EP1898973 B1 relates to an apparatus for the testing of filters aimingto avoid use of high pressures in the hydraulic circuit connected to theultrafilter. In particular, this document shows a method of testingultrafilters comprising generating an overpressure on one side of theultrafilter membrane and a negative pressure on the opposite sidethereof.

Although the above methods have been used in the past, the Applicantconsidered that the state of the art may still be improved.

An aim of the invention is to provide a method and an apparatus fortesting ultrafilters, which improves test rapidity without compromisingtest reliability.

A further aim of the invention is to offer a method and an apparatussuitable for testing ultrafilters of apparatus for extracorporeal bloodtreatment, such as hemodialysis, hemofiltration or hemodiafiltrationapparatus.

An additional aim of the present invention is to make available aprecise and sensitive method and apparatus for testing ultrafilterswhich is able to distinguish over different types of ultrafiltermembrane integrity problems.

SUMMARY

At least one of the above objects is substantially reached by anapparatus according to one or more of the appended apparatus claims.

At least one of the above objects is substantially reached by a methodaccording to one or more of the appended method claims.

Apparatus and methods according to aspects of the invention and capableof achieving one or more of the above objects are here below described.

A 1st aspect concerns an extracorporeal blood treatment apparatus (1)comprising:

-   a supply line (2) having an inlet end connectable to a source of    treatment liquid and an outlet end connectable to an inlet port of a    blood treatment device (5);-   a waste line (13) having an inlet end connectable to an outlet port    the blood treatment device (5) and an outlet end connectable to a    discharge of used treatment liquid, wherein the supply line (2) and    the waste line (13) are part of an hydraulic circuit (100);-   an ultrafilter (19) inserted in the supply line (2) and having a    semipermeable membrane dividing the ultrafilter (19) into a first    chamber (21) and a second chamber (22), the ultrafilter (19)    presenting:    -   a first port connecting a first tract (24) of the supply line        (2) to the first chamber (21),    -   a second port connecting the second chamber (22) to a second        tract (26) of the supply line (2);-   an air inlet line (30) connected to the first chamber (21) of the    ultrafilter (19) or to the first tract (24) of the supply line (2);-   at least one waste pump (34, 38) on the waste line (13);-   at least one pressure sensor (41) configured for detecting pressure    in one of:    -   the second chamber (22) of the ultrafilter (19),    -   the second tract (26) of the supply line (2),    -   the waste line (13);-   a controller (50) connected to the waste pump (34, 38) and the at    least one pressure sensor (41) and configured to carry out an    integrity test procedure comprising the following steps:    -   causing filling of the first chamber (21) of the ultrafilter        (19) with air,    -   after filling the first chamber (21) with air, increasing a        negative pressure or creating a negative pressure (i.e. either        making more negative the pressure relative to atmospheric        pressure present in the ambient where the apparatus (1) is        installed or creating a pressure negative relative to said        atmospheric pressure present in the ambient where the apparatus        (1) is installed) in the second chamber (22) of the ultrafilter        (19) by operating the waste pump (34, 38),    -   verifying, while the waste pump (34, 38) is running, if the        pressure sensed by the at least one pressure sensor (41) reaches        a set negative pressure threshold (Pt) ,    -   determining that the ultrafilter (19) semipermeable membrane has        a multi-fiber break if pressure sensed by the at least one        pressure sensor (41) during said verification step reaches said        set negative pressure threshold (Pt) within a set time interval        (T).

For example the air inlet line may include at least one of an air valveand an air pump connected to the controller (50); the step of causingfilling of the first chamber of the ultrafilter comprises execution bythe controller (50) of at least one of commanding opening of the airvalve and commanding operation of the air pump.

In a 2nd aspect according to the 1st aspect the hydraulic circuit isconfigurable according to a by-pass configuration, where the supply line(2) is in fluid communication with the waste line (13) via a bypass linebypassing the blood treatment device (5) and directly connecting theoutlet end of the supply line (2) and the inlet end of the waste line(13), and according to a normal configuration, where the outlet end ofthe supply line (2) communicates with the inlet end of the waste line(13) through the blood treatment device (5).

In a 3rd aspect according to the 2nd aspect the controller (50) isconfigured to carry out said integrity test procedure comprising withthe hydraulic circuit (100) in by-pass configuration.

In a 4th aspect according to any one of the preceding aspects saidintegrity test procedure, which the controller (50) is configured toexecute, comprises operating the waste pump (34, 38) in closed-loop asfollows:

-   during said step of filling the first chamber (21) of the    ultrafilter (19) with air, achieved by at least opening an air valve    or operating an air pump operative on the air inlet line (30), also    operating the waste pump (34, 38) based on a first set negative    pressure value (P1) which is a desired set value to be reached by    pressure sensed by the at least one pressure sensor (41),-   after said step of filling the first chamber (21) of the ultrafilter    (19) with air, once the first chamber (21) has been emptied from    liquid and filled with air, operating the waste pump (34, 38) based    on a second set negative pressure value (P2), different from the    first set value (P1) and which represents a second desired set value    to be reached by pressure sensed by the at least one pressure sensor    (41).

In a 5th aspect according to the 4th aspect, the second set negativepressure value (P2) is more negative than the first pressure value.

In a 6th aspect according to the 4th or the 5th aspect the set negativepressure threshold (Pt), which is checked during said verifying step,has a negative value intermediate between said first set pressure value(P1) and said second set pressure value (P2) .

In a 7th aspect according to any one of the preceding three aspects thefirst set pressure value (P1) is selected in a pressure range between-150 and -450 mm Hg mmHg.

In an 8th aspect according to any one of the preceding four aspects, thesecond set pressure value (P2) is selected in a pressure range between -300 and - 700 mm Hg mmHg.

In 9th aspect according to any one of the preceding five aspects thesecond pressure value is at least 100 mm Hg mmHg more negative than thefirst set pressure value.

In a 10th aspect according to any one of the preceding aspects theextracorporeal blood treatment apparatus (1) comprises a fresh fluidpump positioned on:

-   the air inlet line (30), or-   the first tract (24) of the supply line (2), between the air    injection point and the first port of the ultrafilter (19) .

In an 11th aspect according to the preceding aspect the controller (50)is also connected to the fresh fluid pump and configured to operate thefresh fluid pump during said step of filling the first chamber (21) ofthe ultrafilter (19) with air.

In a 12th aspect according to the preceding aspect wherein thecontroller is configured to open the air valve (31) with a delay fromstart of operation of the fresh fluid pump.

In a 13th aspect according to any one of the preceding three aspects,wherein the apparatus (1) comprises a safety pressure sensor (90)located between fresh fluid pump (32) and the first chamber of theultrafilter (19), wherein the controller (50) is configured to stopoperation of fresh fluid pump (32) if a pressure difference or pressureratio between pressure detected by pressure sensor (41) and pressuredetected by safety pressure sensor (90) exceeds an identified safetythreshold.

In a 14th aspect according to any one of the preceding aspects, whereinthe integrity test procedure comprises the following further steps whichthe controller (50) is configured to execute:

-   hydraulically isolating the ultrafilter (19);-   receiving pressure values detected by the at least one pressure    sensor (41) at the end of a given transitory period after having    hydraulically isolated the ultrafilter (19) ;-   verifying if two stability conditions are met:    -   pressure values detected by the at least one pressure sensor        (41) at the end of the transitory period are below an auxiliary        negative pressure threshold (Pt 2), and    -   a variation by unit of time (dP/dt) of said pressure values        detected by the at least one pressure sensor (41) at the end of        the transitory period is below a set pressure differential (ΔP),-   determining that the semipermeable membrane of the ultrafilter (19)    has a multi-fiber break if said two stability conditions are not    both met.

The further steps described above may be executed by the controllerafter the steps of the preceding aspects.

In a 15th aspect according to the preceding aspect the auxiliarynegative pressure threshold (Pt 2) is -350 mmHg.

In a 16th aspect according to any one of the preceding two aspects theset pressure differential (ΔP) is 4 mmHg/s.

In a 17th aspect according to any one of the preceding three aspects theauxiliary negative pressure threshold (Pt 2) is less negative than thepressure threshold (Pt).

In an 18th aspect according to any one of the preceding four aspects thecontroller (50) is configured to determine said variation by unit oftime (dP/dt) assigning a respective weight to each received pressurevalue, with the pressure values received during an initial phase ofdetection having more weight than pressure values received during anending phase of detection.

In a 19th aspect according to any one of the preceding aspects theintegrity test procedure comprises the following further steps which thecontroller (50) is configured to execute:

-   hydraulically isolating the ultrafilter (19);-   receiving pressure values detected by the at least one pressure    sensor (41) during a further test interval after a/said transitory    period following hydraulic isolation of the ultrafilter (19),-   verifying if a variation by unit of time (dP/dt) of said pressure    values detected by the at least one pressure sensor (41) during the    further test interval remains below a further set pressure    differential (Δp2) for at least a portion of said test interval,-   determining that the semipermeable membrane of the ultrafilter (19)    has a single-fiber break if the above last verifying step is not    positively passed.

The further steps described above may be executed by the controllerafter the steps of the preceding aspects.

In a 20th aspect according to the preceding aspect the step of verifyingif a variation by unit of time (dP/dt) of said pressure values detectedby the at least one pressure sensor (41) during the further testinterval remains below a further set pressure differential (Δp2) for atleast a portion of said test interval comprises verifying if thevariation by unit of time (dP/dt) of said pressure values detected bythe at least one pressure sensor (41) during the further test intervalremains below 2 mmHg/s for 4 seconds in the first 10 seconds of thefurther test interval.

In a 21st aspect according to any one of the preceding two aspects, saidfurther set pressure differential (Δp2) is a fraction of said setpressure differential (ΔP).

In a 22nd aspect according to any one of the preceding three aspects,said further set pressure differential (Δp2) is less than 70% of saidset pressure differential (ΔP).

In a 23rd aspect according to any one of the preceding four aspects,said further set pressure differential (Δp2) is less than or equal to50% of said set pressure differential (ΔP).

In a 24th aspect according to any one of the preceding five aspects, theapparatus (1) further comprises:

-   at least one inlet valve (39) on the supply line (2) to selectively    open and close supply of liquid from the source of treatment liquid;-   at least one outlet valve (40) on the waste line (13) to selectively    open and close flow of used treatment liquid to the discharge;-   a flush line (28) connecting a third port of the first chamber (21)    of the ultrafilter (19) to the waste line (13), and-   at least one flush valve (29) positioned on the flush line to    selectively open and close the first chamber (21) of the ultrafilter    (19) to the waste line (13).

In a 25th aspect according to the preceding aspect the step ofhydraulically isolating the ultrafilter (19) comprises the followingsub-steps which the controller (50) is configured to execute:

-   closing at least said inlet valve, outlet valve, flush valve and    optionally the air inlet valve,-   stopping the waste pump (34, 38).

In a 26th aspect according to the preceding aspect wherein step ofhydraulically isolating the ultrafilter (19) comprises also stopping thefresh fluid pump (32).

In a 27th aspect according to any one of the preceding aspects theapparatus also comprises an auxiliary ultrafilter (70) inserted in thesecond tract (26) of the supply line (2) and having a semipermeablemembrane dividing the auxiliary ultrafilter (70) into a respective firstchamber (72) and a respective second chamber (73), the auxiliaryultrafilter (70) presenting:

-   a first port connecting a first portion (26 a) of the second tract    (26) of the supply line (2) to the first chamber (72) of the    auxiliary ultrafilter (70),-   a second port connecting the second chamber (73) of the auxiliary    ultrafilter (70) to a second portion (26 b) of the second tract (26)    of the supply line (2);-   an auxiliary air inlet line (76) connected to the first chamber (72)    of the auxiliary ultrafilter (70) or to the first portion (26 a) of    the second tract (26) of the supply line (2);-   an auxiliary air valve or an auxiliary air pump (77) on the air    inlet line (76).

In a 28th aspect according to the preceding aspect, the at least onepressure sensor (41) is configured for detecting pressure in one of:

-   the second chamber (73) of the auxiliary ultrafilter (70) ,-   the second portion (26 b) of the second tract (26) of the supply    line (2),-   the waste line (13).

In a 29th aspect according to any one of the preceding two aspects thecontroller (50) is configured to carry out an auxiliary integrity testprocedure comprising the following steps:

-   causing filling of the first chamber (72) of the auxiliary    ultrafilter (70) with air by operating the waste pump (34 and 38);    this step may also include execution by the controller (50) of at    least one of commanding opening of an auxiliary air valve or    operation of an auxiliary air pump (77) operative on the air inlet    line (76),-   after filling the first chamber (72) of the auxiliary ultrafilter    (70) with air, increasing a negative pressure (rendering the    pressure more negative relative to atmospheric pressure present in    the environment where the apparatus is installed)in the second    chamber (73) of the auxiliary ultrafilter (70) by continuing to    operate the waste pump (34, 38),-   verifying, while the waste pump (34, 38) is running, if the pressure    sensed by the at least one pressure sensor (41) reaches a set    negative pressure threshold (Pt′),-   determining that the auxiliary ultrafilter (70) semipermeable    membrane has a multi-fiber break if the pressure sensed by the at    least one pressure sensor (41) during said verification step does    not reach said set negative pressure threshold (Pt′) within an    auxiliary set time interval (T′).

In a 30th aspect according to the preceding aspect the controller (50)is configured to carry out the auxiliary integrity test procedure withthe hydraulic circuit, i.e., the supply line (2) and the waste line(13), in by-pass configuration.

In a 31st aspect according to any one of the preceding two aspects saidauxiliary integrity test procedure, which the controller (50) isconfigured to execute, comprises operating the waste pump (34, 38) inclosed-loop as follows:

-   during said step of filling the first chamber (72) of the auxiliary    ultrafilter (70) with air, the controller (50) controls operation of    the waste pump (34, 38) based on a first set negative pressure value    (P1′), which shall be reached by pressure sensed by the at least one    pressure sensor (41),-   after said step of filling the first chamber (72) of the auxiliary    ultrafilter (70), once the first chamber (72) has been completely    emptied from liquid and filled with air, the controller (50)    controls operation of the waste pump (34, 38) based on a second set    negative pressure value (P2′), which shall be reached by pressure    sensed by the at least one pressure sensor (41) and which is    different from the first pressure value

In a 32nd aspect according to the preceding aspect the set negativepressure threshold (Pt′) has a negative value intermediate between saidfirst set pressure value (P1′) and said second set pressure value (P2′).

In a 33rd aspect according to any one of the preceding two aspects thefirst set pressure value (P1′) is selected in a pressure range between-150 and -450 mm Hg.

In a 34th aspect according to any one of the preceding three aspects thesecond set pressure value (P2′) is selected in the range between -300and -700 mm Hg mmHg.

In a 35th aspect according to any one of the preceding four aspects thesecond pressure value (P2′) is at least 100 mm Hg mmHg more negativethan the first set pressure value (P1′).

In a 36th aspect according to any one of the preceding five aspects theset negative pressure threshold (Pt′) is selected to have a value whichis intermediate between the first and second pressure values (Pl′, P2′).

In a 37th aspect according to any one of the preceding six aspects thecontroller (50) is configured to check a time related parameter, whichis one of:

-   a time necessary to reach the first pressure value (P1′),-   a rotation frequency of the waste pump (34, 38),-   a pump rotation period of the waste pump (34, 38), and to compare    this detected time related parameter with a corresponding reference    threshold, assigning the identification of a multi-fiber break    problem in membrane (20) of ultrafilter (19) if the check on the    time related parameter is not passed.

In a 38th aspect according to any one of the preceding nine aspects theauxiliary integrity test procedure comprises the following further stepswhich the controller (50) is configured to execute:

-   hydraulically isolating the auxiliary ultrafilter (70);-   receiving pressure values detected by the at least one pressure    sensor (41) at the end of a given transitory period after having    hydraulically isolated the auxiliary ultrafilter (70);-   verifying if two stability conditions are met:    -   pressure values detected by the at least one pressure sensor        (41) at the end of the transitory period are below an auxiliary        negative pressure threshold,    -   a variation by unit of time (dP/dt) of said pressure values        detected by the at least one pressure sensor (41) at the end of        the transitory period is below a set pressure differential,-   determining that the semipermeable membrane of the auxiliary    ultrafilter (70) has a multi-fiber break if said two stability    conditions are not both met.

In a 39th aspect according to the preceding aspect the auxiliarynegative pressure threshold is -350 mmHg.

In a 40th aspect according to any one of the preceding two aspects theset pressure differential is 4 mmHg/s.

In a 41st aspect according to any one of the preceding three aspects thevariation by unit of time (dP/dt) is determined by assigning arespective weight to each received pressure value, with the pressurevalues received during an initial phase of detection having more weightthan pressure values received during an ending phase of detection.

In a 42nd aspect according to any one of the preceding thirteen aspectsthe auxiliary integrity test procedure comprises the following furthersteps which the controller (50) is configured to execute:

-   hydraulically isolating the auxiliary ultrafilter (70);-   receiving pressure values detected by the at least one pressure    sensor (41) during a further test interval subsequent to the    transitory period following hydraulic isolation of the auxiliary    ultrafilter (70),-   verifying if a variation by unit of time (dP/dt) of said pressure    values detected by the at least one pressure sensor (41) during the    further test interval remains below a further set pressure    differential (Op 2′), for example below 2 mmHg/s, for at least a    portion of said further test interval, for example for 4s in the    first 10s of the further test interval,-   determining that the semipermeable membrane of the ultrafilter (70)    has a single-fiber break if the above last verifying step is not    positively passed.

In a 43rd aspect according to the preceding aspect the further setpressure differential (Op 2′) is 2 mmHg/s.

In a 44th aspect according to any one of the preceding six aspects theapparatus further includes:

-   an auxiliary flush line (86) connecting a third port of the first    chamber (72) of the auxiliary ultrafilter (70) to the waste line    (13), and-   an auxiliary flush valve (88) positioned on the flush line to    selectively open and close the first chamber (72) of the auxiliary    ultrafilter (70) to the waste line (13); wherein the step of    hydraulically isolating the auxiliary ultrafilter (70) comprises the    following sub-steps which the controller (50) is configured to    execute:-   at least closing said inlet valve (39), outlet valve (40), auxiliary    flush valve (88), and optionally the air inlet valve and the    auxiliary air inlet valve,-   stopping the waste pump (34 and 38) and, when a fresh fluid pump is    present also stopping the fresh fluid pump (32).

A 45th aspect concerns a method of testing the integrity of anultrafilter membrane of an ultrafilter (19; 70), wherein the ultrafiltermembrane separates the ultrafilter (19; 70) into a first and a secondchamber (21, 22; 72, 73).

A 46th aspect concerns a method of testing the integrity of anultrafilter membrane of at least one ultrafilter (19; 70) of theextracorporeal blood treatment apparatus (1) according to any one ofaspects from the 1st to the 44th.

In a 47th aspect according to any one of the preceding two aspects themethod comprising executing the following steps:

-   emptying the first chamber (21; 72) of the ultrafilter (19; 70) from    liquid and filling the first chamber (21; 72) with air,-   after the first chamber (21; 72) has been filled with air, continue    extracting liquid from the second chamber (22; 73) of the    ultrafilter (19; 70),-   verifying, while extracting liquid from the second chamber (22; 73)    of the ultrafilter (19; 70), if the pressure in the ultrafilter (19;    70) second chamber (22; 73) reaches a set negative pressure    threshold (Pt, Pt′),-   determining that the ultrafilter (19; 70) semipermeable membrane has    a multi-fiber break if the pressure in the second chamber (22; 73)    during the step of extracting liquid does not reach (i.e., does not    go down enough to reach) said set negative pressure threshold (Pt;    Pt′) within a set time interval.

In a 48th aspect according to any one of the preceding three aspects themethod comprises the following further steps:

-   hydraulically isolating the ultrafilter (19; 70);-   waiting a given transitory period;-   verifying if two stability conditions are met:    -   values of pressure in the second chamber (22; 73) of the        ultrafilter (19; 70) at the end of the transitory period are        below an auxiliary negative pressure threshold, for example        below -350 mmHg, and    -   a variation by unit of time (dP/dt) of said pressure values in        the second chamber (22; 73) of the ultrafilter (19; 70) at the        end of the transitory period is below a set pressure        differential, for example below 4 mmHg/s,-   determining that the semipermeable membrane of the ultrafilter (19;    70) has a multi-fiber break if said two stability conditions are not    both met.

The further steps described above may be executed after the steps of thepreceding aspect.

In a 49th aspect according to the preceding aspect the variation by unitof time (dP/dt) is determined by assigning a respective weight to eachreceived pressure value, with the pressure values received during aninitial phase of detection having more weight than pressure valuesreceived during an ending phase of detection.

In a 50th aspect according to any one of the preceding five aspects themethod comprises the following further steps:

-   hydraulically isolating the ultrafilter (19; 70);-   optionally waiting a given transitory period;-   verifying if a variation by unit of time (dP/dt) of values of    pressure during a further test interval remains below a further set    pressure differential,-   determining that the semipermeable membrane of the ultrafilter (19;    70) has a single-fiber break if the above last verifying step is not    positively passed.

The further steps described above may be executed after the steps of thepreceding aspects 47th or 48th or 49th.

In a 51st aspect according to the preceding aspect verifying if avariation by unit of time (dP/dt) of values of pressure during a furthertest interval remains below a further set pressure differentialcomprises verifying if a variation by unit of time (dP/dt) of values ofpressure during a further test interval remains below 2 mmHg/s for atleast 4 seconds in the first 10 seconds of the further test interval.

In a 52nd aspect according to any one of the preceding five aspects,wherein the method comprises the step of checking a time relatedparameter, which is one of:

-   a time necessary to reach a first pressure value (P1′),-   a rotation frequency of the waste pump (34, 38),-   a pump rotation period of the waste pump (34, 38), and to compare    this detected time related parameter with a corresponding reference    threshold, assigning the identification of a multi-fiber break    problem in membrane (20) of ultrafilter (19) if the check on the    time related parameter is not passed.

A 53rd aspect concerns an extracorporeal blood treatment apparatus (1)comprising:

-   a supply line (2) having an inlet end connectable to a source of    treatment liquid and an outlet end connectable to an inlet port of a    blood treatment device (5);-   a waste line (13) having an inlet end connectable to an outlet port    the blood treatment device (5) and an outlet end connectable to a    discharge of used treatment liquid, wherein the supply line (2) and    the waste line (13) are part of an hydraulic circuit (100);-   an ultrafilter (19) inserted in the supply line (2) and having a    semipermeable membrane dividing the ultrafilter (19) into a first    chamber (21) and a second chamber (22), the ultrafilter (19)    presenting:    -   a first port connecting a first tract (24) of the supply line        (2) to the first chamber (21),    -   a second port connecting the second chamber (22) to a second        tract (26) of the supply line (2);-   an air inlet line (30) connected to the first chamber (21) of the    ultrafilter (19) or to the first tract (24) of the supply line (2);-   at least one waste pump (34, 38) on the waste line (13);-   at least one pressure sensor (41) configured for detecting pressure    in one of:    -   the second chamber (22) of the ultrafilter (19),    -   the second tract (26) of the supply line (2),    -   the waste line (13);-   a controller (50) connected to the waste pump (34, 38) and the at    least one pressure sensor (41) and configured to carry out an    integrity test procedure comprising the following steps:    -   filling the first chamber (21) of the ultrafilter (19) with air,        optionally by at least commanding opening an air valve or        operation an air pump located on the air inlet line (30),    -   increasing the negative pressure (i.e., rendering the pressure        more negative relative to atmospheric pressure present in the        environment where the apparatus is installed) or creating a        negative pressure (again relative to said atmospheric pressure)        in the second chamber (22) of the ultrafilter (19) by operating        the waste pump (34, 38), hydraulically isolating the ultrafilter        (19),    -   receiving pressure values from the at least one pressure sensor        (41),    -   determining a variation by unit of time (dP/dt) of said pressure        values detected by the at least one pressure sensor (41) after        having hydraulically isolated the ultrafilter (19),    -   establishing whether the semipermeable membrane of the        ultrafilter (19) has either a single fiber break or a        multi-fiber break based on said variation by unit of time        (dP/dt) of said pressure values detected by the at least one        pressure sensor (41).

In a 54th aspect according to the preceding 1st the hydraulic circuit isconfigurable according to a by-pass configuration, where the supply line(2) is in fluid communication with the waste line (13) via a bypass linebypassing the blood treatment device, and according to a normalconfiguration, where the outlet end of the supply line (2) communicateswith the inlet end of the waste line (13) through the blood treatmentdevice (5) .

In a 55th aspect according to the preceding aspect the controller (50)is configured to carry out said integrity test procedure comprising withthe hydraulic circuit (100) in by-pass configuration.

In a 56th aspect according to any one of the preceding three aspectssaid integrity test procedure, which the controller (50) is configuredto execute, comprises operating the waste pump (34, 38) in closed-loopas follows:

-   during said step of filling the first chamber (21) of the    ultrafilter (19) with air, achieved by at least opening an air valve    or operating an air pump operative on the air inlet line (30), also    operating the waste pump (34, 38) based on a first set negative    pressure value (P1) which is a desired set value to be reached by    pressure sensed by the at least one pressure sensor (41),-   after said step of filling the first chamber (21) of the ultrafilter    (19) with air, once the first chamber (21) has been emptied from    liquid and filled with air, operating the waste pump (34, 38) based    on a second set negative pressure value (P2), different from the    first set value (P1) and which represents a second desired set value    to be reached by pressure sensed by the at least one pressure sensor    (41).

In a 57th aspect according to the 56th aspect, the second set negativepressure value (P2) is more negative than the first pressure value (P1).For example the first set pressure value (P1) is selected in a pressurerange between -150 and -450 mm Hg mmHg and the second set pressure value(P2) is selected in a pressure range between - 300 and - 700 mm Hg mmHg.

In a 58th aspect according to any one of the preceding four aspects theextracorporeal blood treatment apparatus (1) comprises a fresh fluidpump positioned on:

-   the air inlet line (30), or-   the first tract (24) of the supply line (2), between the air    injection point and the first port of the ultrafilter (19) .

In an 59th aspect according to the preceding aspect the controller (50)is also connected to the fresh fluid pump and configured to operate thefresh fluid pump during said step of filling the first chamber (21) ofthe ultrafilter (19) with air.

In a 60th aspect according to the preceding aspect wherein thecontroller is configured to open the air valve (31) with a delay fromstart of operation of the fresh fluid pump.

In a 61st aspect according to any one of the preceding three aspects,wherein the apparatus (1) comprises a safety pressure sensor (90)located between fresh fluid pump (32) and the first chamber of theultrafilter (19), wherein the controller (50) is configured to stopoperation of fresh fluid pump (32) if a pressure difference or pressureratio between pressure detected by pressure sensor (41) and pressuredetected by safety pressure sensor (90) exceeds an identified safetythreshold.

In a 62nd aspect according to any one of the preceding nine aspects thestep of establishing whether the membrane of the ultrafilter (19) haseither a single fiber break or a multi-fiber break based on saidvariation by unit of time (dP/dt) of said pressure values detected bythe at least one pressure sensor (41) comprises the following firstsub-steps:

-   verifying if two stability conditions are met:    -   pressure values detected by the at least one pressure sensor        (41), optionally at the end of a transitory period subsequent to        hydraulic isolation, are below an auxiliary negative pressure        threshold (Pt 2), and    -   the variation by unit of time (dP/dt) of said pressure values        detected by the at least one pressure sensor (41), optionally at        the end of the transitory period is below a set pressure        differential (AP),-   determining that the semipermeable membrane of the ultrafilter (19)    has a multi-fiber break if said two stability conditions are not    both met.

In a 63rd aspect according to the preceding aspect the auxiliarynegative pressure threshold (Pt 2) is -350 mmHg.

In a 64th aspect according to any one of the preceding two aspects theset pressure differential (AP) is 4 mmHg/s.

In an 65th aspect according to any one of the preceding three aspectsthe controller (50) is configured to determine said variation by unit oftime (dP/dt) assigning a respective weight to each received pressurevalue, with the pressure values received during an initial phase ofdetection having more weight than pressure values received during anending phase of detection.

In a 66th aspect according to any one of the preceding four aspects thestep of establishing whether the membrane of the ultrafilter (19) haseither a single fiber break or a multi-fiber break based on saidvariation by unit of time (dP/dt) of said pressure values detected bythe at least one pressure sensor (41) comprises the following secondsub-steps:

-   verifying if a variation by unit of time (dP/dt) of said pressure    values detected by the at least one pressure sensor (41), during a    further test interval, remains below a further set pressure    differential (Op 2) for at least a portion of said test interval,-   determining that the semipermeable membrane of the ultrafilter (19)    has a single-fiber break if the above last verifying step is not    positively passed.

In a 67th aspect according to the preceding aspect, the controller isconfigured to execute the second subs-steps after the first sub-steps.

In a 68th aspect according to any one of the preceding two aspects thestep of verifying if a variation by unit of time (dP/dt) of saidpressure values detected by the at least one pressure sensor (41) duringthe further test interval remains below a further set pressuredifferential (Op 2) for at least a portion of said test intervalcomprises verifying if the variation by unit of time (dP/dt) of saidpressure values detected by the at least one pressure sensor (41) duringthe further test interval remains below 2 mmHg/s for 4 seconds in thefirst 10 seconds of the further test interval.

In a 69th aspect according to any one of the preceding three aspects,said further set pressure differential (Op 2) is a fraction of said setpressure differential (AP).

In a 70th aspect according to any one of the preceding four aspects,said further set pressure differential (Op 2) is less than 70% of saidset pressure differential (AP).

In a 71st aspect according to any one of the preceding five aspects,said further set pressure differential (Op 2) is less than or equal to50% of said set pressure differential (AP).

In a 72nd aspect according to any one of the preceding aspects from the53rd to the 71st, the apparatus (1) further comprises:

-   at least one inlet valve (39) on the supply line (2) to selectively    open and close supply of liquid from the source of treatment liquid;-   at least one outlet valve (40) on the waste line (13) to selectively    open and close flow of used treatment liquid to the discharge;-   a flush line (28) connecting a third port of the first chamber (21)    of the ultrafilter (19) to the waste line (13), and-   at least one flush valve (29) positioned on the flush line to    selectively open and close the first chamber (21) of the ultrafilter    (19) to the waste line (13).

In a 73rd aspect according to the preceding aspect the step ofhydraulically isolating the ultrafilter (19) comprises the followingsub-steps which the controller (50) is configured to execute:

-   closing at least said inlet valve, outlet valve, flush valve and    optionally the air inlet valve,-   stopping the waste pump (34, 38).

In a 74th aspect according to the preceding aspect wherein the step ofhydraulically isolating the ultrafilter (19) comprises also stopping thefresh fluid pump (32).

A 75th aspect concerns a method of testing the integrity of anultrafilter membrane of an ultrafilter (19; 70), wherein the ultrafiltermembrane separates the ultrafilter (19; 70) into a first and a secondchamber (21, 22; 72, 73).

A 76th aspect concerns a method of testing the integrity of anultrafilter membrane of at least one ultrafilter (19; 70) of theextracorporeal blood treatment apparatus (1) according to any one of thepreceding aspects from the 1st to the 44th or from the 53rd to the 75th.

In a 77th aspect according to any one of the preceding two aspects,wherein the method comprises executing the following steps:

-   emptying the first chamber (21; 72) of the ultrafilter (19; 70) from    liquid and filling the first chamber (21; 72) with air,-   after the first chamber (21; 72) has been filled with air, continue    extracting liquid from the second chamber (22; 73) of the    ultrafilter (19; 70),-   hydraulically isolating the ultrafilter (19; 70),-   optionally waiting a given transitory period after hydraulic    isolation,-   receiving pressure values relating to pressure present in the    ultrafilter second chamber,-   determining a variation by unit of time (dP/dt) of said pressure    values detected after having hydraulically isolated the ultrafilter    (19),-   establishing whether the semipermeable membrane of the ultrafilter    (19) has either a single fiber break or a multi-fiber break based on    said variation by unit of time (dP/dt) of said pressure values.

In a 78th aspect according to the preceding aspect, the step ofestablishing whether the membrane of the ultrafilter (19) has either asingle fiber break or a multi-fiber break based on said variation byunit of time (dP/dt) of said pressure values comprises the followingfirst sub-steps:

-   verifying if two stability conditions are met:    -   values of pressure in the second chamber (22; 73) of the        ultrafilter (19; 70) at the end of the transitory period are        below an auxiliary negative pressure threshold, for example        below -350 mmHg, and    -   a variation by unit of time (dP/dt) of said pressure values in        the second chamber (22; 73) of the ultrafilter (19; 70) at the        end of the transitory period is below a set pressure        differential, for example below 4 mmHg/s,-   determining that the semipermeable membrane of the ultrafilter (19;    70) has a multi-fiber break if said two stability conditions are not    both met.

In a 79th aspect according to the preceding aspect the variation by unitof time (dP/dt) is determined by assigning a respective weight to eachreceived pressure value, with the pressure values received during aninitial phase of detection having more weight than pressure valuesreceived during an ending phase of detection.

In a 80th aspect according to any one of the preceding three aspects,the step of establishing whether the membrane of the ultrafilter (19)has either a single fiber break or a multi-fiber break based on saidvariation by unit of time (dP/dt) of said pressure values comprises thefollowing second sub-steps:

-   verifying if a variation by unit of time (dP/dt) of values of    pressure during a further test interval remains below a further set    pressure differential,-   determining that the semipermeable membrane of the ultrafilter (19;    70) has a single-fiber break if the above last verifying step is not    positively passed.

In a 81st aspect according to the preceding aspect verifying if avariation by unit of time (dP/dt) of values of pressure during a furthertest interval remains below a further set pressure differentialcomprises verifying if a variation by unit of time (dP/dt) of values ofpressure during a further test interval remains below 2 mmHg/s for atleast 4 seconds in the first 10 seconds of the further test interval.

In an 82nd aspect according to any one of the preceding aspects eachultrafilter (including if present the auxiliary ultrafilter) is of thetype using a semipermeable membrane formed by a bundle of adjacent andsubstantially coextensive hollow fibers.

In an 83rd aspect according to the preceding aspect the hollow fibersforming the semipermeable membrane are housed in a container and dividethe container inner volume into two chambers: one of the two chambers iscollectively formed by the volume inside the tubular walls of theplurality of fibers, while the other chamber is collectively formed bythe volume outside the tubular walls of the fibers.

DESCRIPTION OF THE DRAWINGS

Aspects of the invention are shown in the attached drawings, which areprovided by way of non-limiting example, wherein:

FIG. 1 shows a schematic layout of a dialysis apparatus implementingaspects of the invention;

FIG. 2 shows a schematic layout of a hemodiafiltration apparatusimplementing aspects of the invention;

FIG. 3 shows a block diagram of a method of testing the integrity of anultrafilter membrane of an ultrafilter, according to aspects of theinvention; and

FIG. 4 shows a block diagram of a method of testing the integrity of anultrafilter membrane of an auxiliary ultrafilter, according to otheraspects of the invention.

DEFINITIONS

In the present description and claims the following definitions areadopted:

-   checking integrity of the ultrafilter (or of the auxiliary    ultrafilter) semipermeable membrane means checking that the    semipermeable membrane does not present one or more breaks in    correspondence of any fiber forming the semipermeable membrane    structure which could compromise the ability of the semipermeable    membrane to properly separate undesired particles such as    pollutants, bacteria, endotoxins, from liquid to be filtered; in    case of ultrafilter semipermeable membranes formed by a bundle of    hollow fibers, checking integrity of the ultrafilter (or of the    auxiliary ultrafilter) semipermeable membrane means checking that    the tubular wall of all fibers forming the ultrafilter membrane are    intact and that therefore the membrane does not present one or more    breaks at any fiber tubular wall;-   single fiber break means a break compromising the membrane integrity    and affecting a single fiber of the ultrafilter membrane;-   multi-fiber break or multi-fiber break problem or multi-fiber breaks    means a plurality of breaks, i.e.: breaks affecting two or more    fibers and compromising the membrane integrity.

CONVENTIONS

In the present description and claims the following conventions areadopted:

-   the terms downstream and upstream respectively refer to the    downstream or upstream position of a component with respect to    another component relative to the direction of a fluid flow in a    line during normal use of the apparatus;-   each pressure value represents the difference between an absolute    pressure value and the absolute value of the atmospheric pressure in    the ambient where the apparatus is placed; thus, assuming the    absolute value of ambient pressure at the apparatus is 760 mmHg, a    negative pressure value of for example -300 mmHg represents an    absolute pressure value which is = 760 - 300 mmHg = 460 mmHg, i.e.,    300 mmHg below the absolute value of the pressure present in the    environment surrounding the apparatus.

DETAILED DESCRIPTION

An apparatus 1 for extracorporeal treatment of blood - which mayimplement innovative aspects of the invention - is shown in FIGS. 1 and2 . In particular, the apparatus 1 of FIG. 1 is a dialysis apparatus,while the apparatus 1 of FIG. 2 is a hemodiafiltration apparatus.

The apparatus 1 of FIGS. 1 and 2 includes hydraulic circuit 100comprising a supply line 2 having an inlet end 3 connectable to a sourceof treatment liquid. The source of treatment liquid is not shown and mayfor example be tap water or water coming from a centralized waterpreparation system. The supply line extends from the inlet end 3 to anoutlet end 4 connectable to an inlet port of a blood treatment device 5.For example, in the example of FIG. 1 the blood treatment device 5comprises a dialyzer, while in the example of FIG. 2 the blood treatmentdevice 5 comprises a hemofilter or a hemodiafilter. Note that thespecific nature of the blood treatment device is not relevant to thepresent invention. The blood treatment device 5 of FIGS. 1 and 2 has ablood chamber 6 and a liquid chamber 7 separated by a semi-permeablemembrane 8: the outlet end 4 of the supply line 2 is connected to aninlet of the liquid chamber 7 of the blood treatment device 5. On theother end, the blood chamber 6 is connected to an extracorporeal bloodcircuit 9 comprising a blood withdrawal line 11 having an end connectedwith an inlet to the blood chamber 6 and a blood return line 10 havingan end connected to an outlet of the blood chamber 6. A blood pump 12may operate on the extracorporeal blood circuit 9 to pump blood from apatient into the blood withdrawal line, through the blood chamber, intothe blood return line and back to the patient. The hydraulic circuit 100of the apparatus 1 of FIGS. 1 and 2 further comprises a waste line 13having an inlet end 14 connected to an outlet port the liquid chamber 7of the blood treatment device 7 and an outlet end 15 connected to adischarge of used treatment liquid. As shown in FIGS. 1 and 2 the supplyline 2 and the waste line 13 are configurable according to a normalconfiguration, where the outlet end 4 of the supply line 2 is connectedto the liquid chamber 7 and in fluid communication with the inlet end 14of the waste line 13. The supply line 2 and the waste line 13 are alsoconfigurable according to a by-pass configuration, where the supply lineis in fluid communication with the waste line via a bypass line 16 (seedashed line 16 in FIGS. 1 and 2 ) bypassing the blood treatment device 5and connecting the outlet end of the supply line with the inlet end ofthe waste line. The switch from the normal to the bypass configurationmay for example be obtained thanks to appropriate valves 17 and 18 orother valves which may be present in the circuit 100. As visible inFIGS. 1 and 2 , the apparatus 1 comprises an ultrafilter 19 inserted inthe supply line 2 and having a respective semipermeable membrane 20dividing the ultrafilter into a first chamber 21 and a second chamber22; the ultrafilter 19 is used for a plurality of treatments and isperiodically changed: the ultrafilter 19 may be subject to the integritytest described below to make sure about integrity of the filter membranebefore the start of each new treatment; the ultrafilter 19 also presentsa first port 23 connecting a first tract 24 of the supply line 2 to thefirst chamber 21: basically the first tract 24 extends from inlet end 3to the first port 23 of the ultrafilter 19; the ultrafilter 19 alsopresents a second port 25 connecting the second chamber 22 to a secondtract 26 of the supply line extending from the second port 25 to theoutlet end 4 of the supply line. The ultrafilter 19 may also present athird port 27 connecting the first chamber 21 to a flushing line 28connectable to the waste line 13: in the examples of FIGS. 1 and 2 , theflushing line 28 has at least a valve 29 for selectively opening andclosing the flushing line and thus selectively forming or stopping afluid communication between the first chamber 21 and the waste line 13.

The apparatus 1 also includes an air inlet line 30: the air inlet lineof the example of FIGS. 1 and 2 is connected to the first tract 24 ofthe supply line 2 at air injection point 33 and presents an air inletvalve 31, which may be selectively opened or closed to respectivelyallow or prevent admission of air into the supply line 2 and towards theultrafilter 19; note that instead or in addition to the air valve 31 anocclusive air pump may be used in order to selectively control admissionof air into the air inlet line 30. Alternatively, the air inlet line 30may be directly connected to the first chamber 21 of the ultrafilter 19.As shown in FIGS. 1 and 2 , the apparatus 1 further comprises a freshfluid pump 32 on the supply line 2 and a waste pump 34 on the waste line13. In the examples shown, the fresh fluid pump 32 is positioned on thefirst tract 24 of the supply line 2, downstream to air injection point33 and upstream the ultrafilter 19. Note that in the examples shown athree-way valve 35 may be positioned at the end of a further by-passline 36 connecting the waste line 13 and the supply line 2:specifically, the three way valve 35 is positioned between the freshfluid pump 32 and the ultrafilter 19, while the further by-pass line 36extends between the three-way valve 35 and a junction point 37 inthe-waste line 13, positioned between the waste pump 34 and the outletend 15 of the waste line.

Also note that the apparatus 1 may comprise an auxiliary waste pump 38operative on the waste line 13 and positioned between the waste pump 34and the outlet end 15 of the waste line. Additionally, a general waterinlet valve 39, operable to selectively open and close admission offresh liquid (fresh water) into the supply line 2, may be present at theinlet end 3 of the supply line 2, and a general waste outlet valve 40,operable to selectively open and close discharge of waste liquid out ofthe waste line 13 may be present at the outlet end of waste line 13.

The apparatus 1 of FIGS. 1 and 2 furthermore comprises one or morepressure sensors as described below. In greater detail, at least onepressure sensor 41 is configured for directly or indirectly detectingpressure in the second chamber of the ultrafilter. At this purpose, thepressure sensor 41 may be directly connected to the second chamber 22 ofthe ultrafilter 19 or it may be positioned on the second tract 26 of thesupply line or on the waste line in correspondence of the tract of wasteline extending between the inlet end 14 and the waste pump 34. As shownin FIGS. 1 and 2 , the apparatus may include an auxiliary waste pump 38and, in this case, an auxiliary pressure sensor 42 is positioned on thewaste line between the waste pump 34 and the auxiliary waste pump 38.

Again with reference to FIGS. 1 and 2 the apparatus may include anoptional water inlet ultrafilter 43, which is operative on the supplyline immediately downstream the water inlet valve 39: also the waterinlet ultrafilter 43 may be periodically changed and, in the exampleherein described, is not subject to any integrity test procedure.

Finally, the apparatus of FIGS. 1 and 2 includes a controller 50. Thecontroller 50 is connected to the valves, pumps and pressure sensorsdescribed above and configured to control operation of the apparatus 1.In detail, the controller 50 is connected to the air valve 31, the wastepump 34, (if present) the waste pump 38, the pressure sensor 41 and (ifpresent) the auxiliary pressure sensor 42. The controller 50 may beconnected to a user interface 51 and be configured to receive inputsfrom an operator and then perform execution of an extracorporeal bloodtreatment based on the operator’s input: the present disclosure does notprovide further details on the controller role in the handling of theblood treatment as this is not relevant to the present invention.

A safety pressure sensor 90 is located between fresh fluid pump 32 andthree-way valve 35. The controller may be configured to stop operationof fresh fluid pump 32 once the pressure difference between pressuredetected by sensor 41 and pressure detected by safety pressure sensor 90exceeds an identified safety threshold to prevent from pressurize air inchamber 21. Of course pressure ratio between pressure detected by sensor41 and pressure detected by safety pressure sensor 90 may be used inplace of pressure difference.

At the beginning of each new treatment, or periodically every givennumber of treatments, the controller 50 is configured to automatically(or upon operator’s request) execute an ultrafilter integrity testprocedure as herein described in further detail. Note that beforeinitiating the ultrafilter integrity test procedure, the controller 50may also be configured or programmed to execute a number of per se knownphases such as coordinating the filling and flushing of the hydrauliccircuit and operate valves 17 and 18 to put the hydraulic circuit and inparticular the supply line and the waste line in a by-pass configuration(see dash lines in FIGS. 1 and 2 by-passing the blood treatment device5).

With the supply line and waste line in the by-pass configuration, thecontroller 50 is configured or programmed to execute an integrity testprocedure for checking whether the membrane 20 of the ultrafilter 19 isintact or not.

With reference now to the flowchart of FIG. 3 , the integrity testprocedure comprises the following steps.

Initially, the controller 50 causes filling with air of the firstchamber 21 of the ultrafilter 19 (step 110 in FIG. 3 ): this is achievedby opening the air valve 31 (or possibly operating the air pump 31) andcreating a suction of air towards said first chamber of the ultrafilter.In order to create an air flow through the air inlet line 30 and towardsthe ultrafilter first chamber 21, the fresh fluid pump 32 and the wastepump 34 are is also operated, for example when opening the air valve oreven before opening the air valve 31 (or in case an air pump 31 is usedwhen operating or before operating the air pump 31). For example, thefresh fluid pump 32 may be operated at a given angular speed while thewaste pump 34 may be operated in closed loop based on a first setpressure P1 which is a desired value to be sensed at the pressure sensor41. In an example, the waste pump 34 may be operated in closed loop withthe first set pressure P1 at pressure sensor 41 set equal to - 350 mmHgas control loop parameter (i.e. 350 mmHg below the atmospheric pressurepresent in the ambient where the apparatus is installed). In a case likein FIGS. 1 and 2 where two pumps are present in the waste line 13, thenboth waste pump 34 and auxiliary waste pump 38 may (during this phase)be operated in closed loop based on the first set desired pressure P1 tobe sensed at the pressure sensor 41 for pump 34 and to be sensed atauxiliary pressure sensor 42 for pump 38. The first set pressure valueP1 (e.g., - 350 mmHg) is in this case the same for both pumps.

After filling the first chamber with air, the controller 50 isconfigured to form a negative pressure or further increase the value ofnegative pressure in the second chamber of the ultrafilter (step 111 inFIG. 3 - as always negative pressure is intended relative to theatmospheric pressure present in the ambient where the machine operates;therefore increasing the value of the negative pressure means making thepressure further below the atmospheric pressure present in theenvironment where the apparatus is installed) by continuing to operatethe waste pump, or the waste pumps if two waste pumps are present. Ingreater detail, after said step of filling the first chamber of theultrafilter, i.e., once the first chamber has been completely emptiedfrom liquid and filled with air, the controller 50 controls operation ofthe waste pump 34 in closed loop based on a second set negative pressurevalue P2 (e.g., -600 mmHg), which shall be reached by pressure sensed bythe pressure sensor 41 and which is more negative than the firstpressure value P1 (again relative to ambient pressure present where theapparatus is installed). In a case like in FIGS. 1 and 2 where two pumpsare present in the waste line 13, then both waste pump 34 and auxiliarywaste pump 38 may (during this phase) be operated in closed loop basedon second set negative pressure value P2 to be sensed at the pressuresensor 41 for pump 34 and to be sensed at auxiliary pressure sensor 42for pump 38.

For example, the first set pressure value P1 may be selected in apressure range between -150 and -450 mm Hg, while the second setpressure value P2 may be selected in the range between -300 and - 700 mmHg (with the condition that the second pressure value be at least 100 mmHg more negative than the first set pressure value).

More in general, the first set pressure value P1 may be selected in apressure range allowing to drain the ultrafilter at moderate flow ratesin order to avoid excessive stress on the membrane; the second setpressure value P2 may be selected such as to have an appreciable deltapressure with no residual flow, thus avoiding excessive stresses on themembrane and degasification that could cause exceeding the membranebubble point (thus resulting into possible false alarms).

After the above described two steps, the controller provides forverifying (step 112 in FIG. 3 ), while the waste pump 34 is running (orboth the waste pump 34 and the waste pump 38 are still running), if thepressure sensed by the pressure sensor 41 reaches a set negativepressure threshold Pt, for then determining (step 113) that theultrafilter semipermeable membrane has a multi-fiber break if thepressure sensed by the pressure sensor 41 during the verification stepdoes not reach the set negative pressure threshold Pt within a set timeinterval T. This verification step may include checking pressure at thepressure sensor 41 after expiration of time interval T; alternativelyone may envisage to measure the time interval at which the negativepressure threshold Pt is reached. In any case, if in this step thethreshold pressure Pt is not reached or reached too late, the controller50 concludes that there is a multi-fiber break problem for the membraneof the ultrafilter 19. The set negative pressure threshold has anegative value intermediate between said first set pressure value andsaid second set pressure value. For example if the first pressure valueis set at -350 mm Hg and the second pressure value is set at - 600 mmHg, the pressure threshold may be equal to - 500 mm Hg. The set pressurethreshold has a negative value aimed at identifying multi-fiber breaks,thus providing an early detection.

The time interval (i.e., the interval by which the pressure sensed bythe pressure sensor 41 should reach the set negative pressure thresholdto exclude a multi-fiber break of the ultrafilter membrane) is countedby the controller starting from the moment at which the controllerimposes the second negative pressure as setting to control the wastepump 34 (or to both waste pumps 34 and 38). This time interval lasts 10to 60 seconds, for example 30 seconds.

According to aspects of the invention, the integrity test procedure mayfurther comprise the following additional steps which the controller isconfigured to execute after steps 110 to 113 described above.

In detail, at step 114 the controller is configured to command theappropriate components for hydraulically isolating the ultrafilter: asit is known to the skilled person hydraulic isolation of the ultrafiltermay take place in different ways depending upon the specific design ofthe hydraulic circuit 100. For example, with reference to FIG. 1 , thecontroller may command closure of at least valves 29, 40 and 35 (orother equivalent valves blocking flow to the first chamber 21) and stopof the pumps 32, 34 and 38. Then, the controller (step 115 in FIG. 3 )is configured for receiving pressure values detected by the pressuresensor 41 at the end of a given transitory period after havinghydraulically isolated the ultrafilter; subsequently, the controller isconfigured for verifying (step 116) if two stability conditions (116 a,116 b) are met, namely that the pressure values detected by pressuresensor 41 at the end of the transitory period be below an auxiliarynegative pressure threshold Pt 2 (for example below -350 mmHg, againrelative to atmospheric pressure present in the ambient where themachine is installed), and that the variation by unit of time (dP/dt) ofthe pressure values detected by the at least one pressure sensor 41 atthe end of the transitory period be sufficiently small and specificallybe below a set pressure differential OP, for example below a valuecomprised between 3 to 6 mmHg, and in a presently preferred variantbelow 4 mmHg/s. Note that in a preferred embodiment the auxiliarynegative pressure threshold Pt 2 is less negative than the pressurethreshold Pt (relative to atmospheric pressure present in the ambientwhere the machine is installed, thus Pt 2 is closer than Pt toatmospheric pressure). Furthermore, the set pressure differential AP ischosen at a value suitable to detect multi-fiber breaks; in addition andin accordance with a further aspect, the controller 50 may be configuredto sample the dP/dt values giving more weight to pressure values at thebeginning of the detection phase when delta pressure is at its highestvalues (for example using a low-pass filter). The controller 50 (step121) is configured for then determining that the semipermeable membraneof the ultrafilter 19 has a multi-fiber break if the two conditions(steps 116 a, 116 b) are not both met.

The integrity test procedure may also comprise the following furthersteps (steps 117-120 in FIG. 3 ) which the controller is configured toexecute in order to determine if the membrane 20 of the ultrafilter 21has a single fiber break. The further steps 117-120 described below are,in one aspect of the invention, executed after having verified thatmembrane 20 of the same ultrafilter 21 has no multi-fiber breaks (steps110-113 and steps 114-116). In other words, the check for a possiblesingle fiber break may be made as last check, thereby avoiding to carryout unnecessary steps if it is concluded that there is a higher rankingproblem, namely a multi-fiber break. According to this aspect, theintegrity test procedure, may therefore be configured to hydraulicallyisolate the (or maintain hydraulic isolation of) ultrafilter 19 and thenreceiving pressure values detected by the pressure sensor 41 during afurther test interval after said transitory period following hydraulicisolation of the ultrafilter. In other words, while steps 114-115 areexecuted after hydraulic isolation of the ultrafilter but duringpressure stabilization, the following steps are executed after havingwaited a relatively long time interval (longer than said transitoryperiod) after which it is expected that, absent fiber integrityproblems, pressure should be highly stable. Thus, the controller 50 isconfigured, after waiting for expiration of the transitory period andduring the further test interval, for verifying if a variation by unitof time (dP/dt) of said pressure values detected by the pressure sensor41 during the further test interval remains below a further set pressuredifferential Op 2 during at least a portion lasting n seconds of thefurther test interval (step 117). The further set pressure differentialOp 2 may be in the range between 1 and 3 mmHg and in a specific exampleit may be equal to 2 mmHg. More in general, the further set pressuredifferential Op 2 is set in order to detect a single broken fiber (Op 2may in practice be a fraction, e.g., 50% compared to said set pressuredifferential AP). The test interval is relatively short and may last 5to 30 seconds, for instance 10 seconds; therefore, the controller checksif dp/dt stays below for example 2 mmHg during a portion of e.g., 4seconds of the test interval (step 117) and also checks expiration ofthe test interval (118); the controller is configured to then establishthat the membrane of the ultrafilter has a single-fiber break (step 119)if the check of step 117 is not positively passed before expiration ofthe test interval (step 118), i.e., before expiration of the 10 secondsin this example. Otherwise, if before expiration of the test interval,dp/dt stays below Op 2 (in this example below 2 mmHg) for n seconds (inthis example for consecutive 4 seconds) , then it is determined that theultrafilter membrane is intact (step 120).

The apparatus of FIG. 2 has, in addition to the ultrafilter 20, anauxiliary ultrafilter 70 inserted in the second tract 26 of the supplyline 2. The auxiliary ultrafilter 70 is used for a plurality oftreatments and is periodically changed: for this reason also ultrafilter70 may be subject to the integrity test described below to make sureabout integrity of the filter membrane before the start of each newtreatment. The auxiliary ultrafilter 70 has a semipermeable membrane 71dividing the auxiliary ultrafilter into a respective first chamber 72and a respective second chamber 73: the auxiliary ultrafilter may bestructurally identical to the ultrafilter 20. The auxiliary ultrafilter70 presents a first port 74 connecting, via first portion 26 a of secondtract 26, the first chamber 72 to second port 25 of the ultrafilter 19second chamber 22. The auxiliary ultrafilter 70 also includes arespective second port 75 connecting the second chamber 73 of theauxiliary ultrafilter 70 to a second portion 26 b of the second tract 26of the supply line 2. It should be noted that in the non-limitingexample of FIG. 2 , an infusion line 81 may depart from the secondportion 26 b of the second tract 26 of line 2: in particular in theexample of FIG. 2 , infusion line 81 departs from bifurcation point 80and may lead to an infusion port 83, which may be present on anaccessible portion of the apparatus 1 (for example on the apparatusfront panel), to which one or more replacement fluid lines 84 and 85 maybe connected. Replacement fluid lines 84 and 85 shown in FIG. 2 therebybring to the extracorporeal blood circuit fresh fluid filtered throughthe ultrafilters 21 and 70. An auxiliary air inlet line 76 is connectedto the first chamber 72 of the auxiliary ultrafilter 70 or to the firstportion 26 a of the second tract of the supply line: the air inlet line76 is provided with a respective auxiliary air valve 77 (or with anauxiliary occlusive air pump) in order to selectively open and closeadmission of air via the air inlet line 76 under the control ofcontroller 50 and allow air filling of the first chamber of theauxiliary ultrafilter during execution of the integrity test procedureof the semipermeable membrane 71. In the alternative embodiment of FIG.2 , pressure sensor 41 may be configured for detecting pressure in oneof the second chamber of the ultrafilter, the second portion of thesecond tract of the supply line, or the waste line (this lastalternative is shown in FIG. 2 ). An auxiliary flush line 86 connects athird port 87 of the first chamber of the auxiliary ultrafilter 70 tothe waste line, and an auxiliary flush valve 88 is positioned on theflush line 86 to selectively open and close the first chamber of theauxiliary ultrafilter 70 to the waste line.

The controller 50 is configured to carry out, with the supply line andthe waste line in by-pass configuration, an auxiliary integrity testprocedure on the auxiliary ultrafilter 70. The auxiliary test procedureon the ultrafilter is also represented in FIG. 4 : in any case moststeps of the auxiliary test procedure are similar to those of the testprocedure conducted on the ultrafilter 20.

In particular, according to the auxiliary integrity test procedure, thecontroller 50 initially causes filling with air of the first chamber 72of the ultrafilter 70 (step 110 in FIG. 4 ): this is achieved by openingthe air valve 77 (or activating an air pump on the auxiliary air inletline) and creating a suction of air towards said first chamber of theultrafilter. In order to create an air flow through the air inlet line76 and towards the ultrafilter first chamber 72, the waste pump 34 orthe waste pumps 34 and 38 is/are operated, for example when opening theair valve or even before opening the air valve 77 (in case an occlusiveair pump is used in place of the air valve the pump 34 or the pumps 34and 38 may be operated in synchronism with the occlusive air pump oreven before starting operation of the occlusive air pump). The wastepump 34 may be operated in closed loop based on a first set pressure P1′which is a desired value to be sensed at the pressure sensor 41. In anexample, the waste pump 34 may be operated in closed loop with the firstset pressure P1′ at pressure sensor 41 set equal to - 300 mmHg ascontrol loop parameter. In a case like in FIG. 2 , where two pumps arepresent in the waste line 13, then both waste pump 34 and auxiliarywaste pump 38 may (during this phase) be operated in closed loop basedon the first set desired pressure P1′ to be sensed at the pressuresensor 41 for pump 34 and to be sensed at auxiliary pressure sensor 42for pump 38. The first set pressure value P1′ (e.g., - 300 mmHg) may bethe same for both pumps.

In case pressure sensor 41 immediately reaches the P1′ first setpressure value, thus causing the waste pump 34 (and if present also pump38) to decelerate or stop without removing the water supposed to bestill present in chamber 72, this identifies that the chamber 72 is inreality already empty. Thus, the controller 50 may also be configured,in accordance with an ancillary aspect, to check a time relatedparameter (step 130) such as the time necessary to reach the firstpressure value P1′ or the pump rotation frequency of waste pump 34(and/or 38), or the pump rotation period of pump 34 (and/or 38), andcompare this detected time related parameter with a correspondingreference threshold, assigning the identification of a multi-fiber breakproblem in membrane 20 of ultrafilter 19 if the check on the timerelated parameter is not passed (step 131). In practice, if the timenecessary to reach the first pressure value P1′ is too short, or if thefrequency of one or both the waste pumps is too high, or if the pumprotation period of one or both the waste pumps is too small, then it isconcluded that there is a multi-fiber break of the membrane 19 ofultrafilter 20, which for some reason was not detected before. Then,after filling the first chamber 72 with air, the controller 50 isconfigured to form a negative pressure or increase the negative pressurein the second chamber 73 of the ultrafilter (step 111 in FIG. 4 -negative pressure is intended relative to the atmospheric pressurepresent in the ambient where the machine operates; therefore increasingthe value of the negative pressure means making the pressure furtherbelow the atmospheric pressure present in the environment where theapparatus is installed) by continuing to operate the waste pump or thewaste pumps if two waste pumps are present. In greater detail, aftersaid step of filling the first chamber of the ultrafilter with air,i.e., once the first chamber has been completely emptied from liquid andfilled with air, the controller 50 controls operation of the waste pump34 in closed loop based on a second set negative pressure value P2′(e.g., - 600 mmHg), which shall be reached by pressure sensed by thepressure sensor 41 and which is more negative than the first pressurevalue P1′. In a case like in FIG. 2 where two pumps are present in thewaste line 13, then both waste pump 34 and auxiliary waste pump 38 may(during this phase) be operated in closed loop based on second setnegative pressure value P2′ to be sensed at the pressure sensor 41 forpump 34 and to be sensed at auxiliary pressure sensor 42 for pump 38.

The first set pressure value P1′ may be selected in a pressure rangebetween -150 and -450 mm Hg, while the second set pressure value P2′ maybe selected in the range between - 300 and - 700 mm Hg (with thecondition that the second pressure value be at least 100 mm Hg morenegative than the first set pressure value).

More in general, the first set pressure value P1′ may be selected in apressure range allowing to drain the ultrafilter at moderate flow ratein order to avoid excessive stress on the membrane; the second setpressure value P2′ may be selected to form a sufficient delta pressurewith no residual flow, also avoiding excessive stress on the membraneand degasification that could cause exceeding the membrane bubble pointexceeding. At the end of the draining phase of ultrafilter 70, thecontroller may be configured to put first port 74 in communication withline 15, for example by opening an ancillary by-pass valve 91 placed ona line connecting the first tract 26 a with the waste line 15. Thecontroller opens the ancillary by-pass valve 91 for a short time frame(e.g., 1 to 5 seconds) to ensure the complete draining of theultrafilter 70 from top to bottom.

After the above described two steps, the controller provides forverifying (step 112 in FIG. 3 ), while the waste pump 34 is running (orboth the waste pump 34 and the waste pump 38 are still running), if thepressure sensed by the pressure sensor 41 reaches a set negativepressure threshold Pt′, for then determining (step 113) that theultrafilter membrane 71 has a multi-fiber break if the pressure sensedby the pressure sensor 41 during the verification step does not reachthe set negative pressure threshold Pt′ within a set time interval T′.This verification step may include checking pressure at the pressuresensor 41 after expiration of time interval T′; alternatively, one mayenvisage to measure the time interval at which the negative pressurethreshold Pt′ is reached. In any case, if in this step the thresholdpressure Pt′ is not reached or reached too late, the controller 50concludes that there is a multi-fiber break problem for thesemipermeable membrane 71 of the ultrafilter 70. The set negativepressure threshold Pt′ has a negative value intermediate between saidfirst set pressure value P1′ and said second set pressure value P2′. Forexample if the first pressure value P1′ is set at -300 mm Hg and thesecond pressure value P2′ at - 600 mm Hg, the pressure threshold Pt′ maybe equal to - 450 mm Hg. In more general terms, the pressure thresholdPt′ may be selected to have a value which is a negative valueintermediate between said first set pressure value P1′ and said secondset pressure value P2′ and which aims at early identification ofmulti-fiber breaks.

The set time interval T′ (i.e., the interval by which the pressuresensed by the pressure sensor 41 should reach the set negative pressurethreshold Pt′ to exclude a multi-fiber break of the ultrafiltermembrane) is counted by the controller starting from the moment at whichthe controller imposes the second negative pressure P2′ as setting tocontrol the waste pump 34 (or to both waste pumps 34 and 38). This timeinterval T′ may last 10 to 60 seconds, for example of 30 seconds.

According to aspects of the invention, the auxiliary integrity testprocedure may further comprise the following additional steps which thecontroller 50 is configured to execute after steps 110 to 113 describedabove.

In detail, at step 114 the controller 50 is configured to command theappropriate components to hydraulically isolating the ultrafilter 70:for example, with reference to FIG. 2 , the controller may commandclosure of valves 35, 40 and 88 (and possibly also valve 77) and stop ofthe pumps 32, 34 and 38. Then, the controller (step 115 in FIG. 4 ) isconfigured for receiving pressure values detected by the pressure sensor41 at the end of a given transitory period after having hydraulicallyisolated the auxiliary ultrafilter 70; subsequently, the controller 50is configured for verifying (step 116) if two stability conditions (116a, 116 b) are met, namely that the pressure values detected by pressuresensor 41 at the end of the transitory period be below an auxiliarynegative pressure threshold Pt2′ (for example below -350 mmHg), and thatthe variation by unit of time (dP/dt) of the pressure values detected bypressure sensor 41 at the end of the transitory period be sufficientlysmall and specifically be below a set pressure differential ΔP′, forexample below 4 mmHg/s. Note that in a preferred embodiment theauxiliary negative pressure threshold Pt2′ is less negative than thepressure threshold Pt′ and the set pressure differential ΔP′ is set inorder to detect multi-fiber breaks (example 4 mmHg); in addition and inaccordance with a further aspect, the controller 50 may be configured tosample the dP/dt values giving more weight to pressure values at thebeginning of the detection phase when delta pressure is at its highestvalues (for example using a low-pass filter). The controller 50 (step121) is configured for then determining that the membrane of theultrafilter 19 has a multi-fiber break if the two conditions (steps 116a, 116 b) are not both met.

The auxiliary integrity test procedure on ultrafilter 70 may alsocomprise the following further steps which the controller is configuredto execute in order to determine if the membrane 71 has a single fiberbreak. The further steps described below are, in one aspect of theinvention, executed after having verified that membrane 70 of the sameultrafilter 71 has no multi-fiber breaks (steps 110-113 and steps114-116). In other words, the check for a possible single fiber breakmay be made as last check on the ultrafilter 70, thereby avoiding tocarry out unnecessary steps if it is concluded that there is a higherranking problem, namely a multi-fiber break. According to this aspect,the integrity test procedure, may therefore be configured tohydraulically isolate (or maintain hydraulic isolation of) the auxiliaryultrafilter 70 and then receiving pressure values detected by thepressure sensor 41 during a further test interval after the transitoryperiod following hydraulic isolation of the ultrafilter 70. In otherwords, while steps 114-115 are executed after hydraulic isolation of theultrafilter 70 but during pressure stabilization, the following stepsare executed after having waited a relatively long transitory periodafter which it is expected that - absent fiber integrity problems -pressure should be highly stable. Thus, the controller 50 is configured,after waiting for expiration of the transitory period, for verifying ifa variation by unit of time (dP/dt) of said pressure values detected bythe pressure sensor 41 during the further test interval remains below afurther set pressure differential Δp2′ during at least a portion lastingn seconds of the further test interval (step 117). The further setpressure differential Δp2′ may be in the range between 1 and 3 mmHg andin a specific example it may be equal to 2 mmHg. More in general, thefurther set pressure differential Δp2′ is set in order to detect asingle broken fiber (Δp2′ may in practice be a fraction, e.g., 50%compared to said set pressure differential ΔP′). The test interval isrelatively short and may last 5 to 30 seconds, for instance 10 seconds;therefore, the controller checks if dp/dt stays below for example 2 mmHgduring a portion of e.g., 4 seconds of the test interval (step 117) andalso checks expiration of the test interval (118); the controller isconfigured to then establish that the membrane of the auxiliaryultrafilter 70 has a single-fiber break (step 119) if the check of step117 is not positively passed before expiration of the test interval(step 118), i.e., before expiration of the 10 seconds in this example.Otherwise, if before expiration of the test interval, dp/dt stays belowΔp2′ (in this example below 2 mmHg) for n seconds (in this example forconsecutive 4 seconds), then it is determined that the auxiliaryultrafilter membrane is intact (step 120).

Controller 50

As already indicated the apparatus according to the invention makes useof at least one controller 50. This controller may comprise a digitalprocessor (CPU) with memory (or memories), an analogical type circuit,or a combination of one or more digital processing units with one ormore analogical processing circuits. In the present description and inthe claims it is indicated that the controller is “configured” or“programmed” to execute certain steps: this may be achieved in practiceby any means which allow configuring or programming the controller. Forinstance, in case of a controller comprising one or more CPUs, one ormore programs are stored in an appropriate memory: the program orprograms containing instructions which, when executed by the controller,cause the controller to execute the steps described and/or claimed inconnection with the controller. Alternatively, if the controller is ofan analogical type, then the circuitry of the controller is designed toinclude circuitry configured, in use, to process electric signals suchas to execute the controller steps herein disclosed.

Method of Testing the Integrity of an Ultrafilter Semipermeable Membrane

The invention also concerns a method of testing the integrity of anultrafilter membrane of an ultrafilter. The ultrafilter may be part ofan extracorporeal blood treatment apparatus. For instance, the methodmay be used for testing the integrity of the membrane of one or all theultrafilters described above in connection with the apparatus of FIG. 1or the apparatus of FIG. 2 . In accordance with one aspect, the methoddescribed below may be implemented by any apparatus 1 described above orclaimed in any one of the appended claims.

The method of the invention detects if the ultrafilter membrane issubject to multi-fiber breaks or to a single fiber break. The methodcomprises executing the following steps (please refer again to FIG. 3and to FIG. 4 ):

-   step 110: emptying the first chamber of the ultrafilter from liquid    and filling the first chamber with air,-   step 111: after the first chamber has been filled with air, continue    extracting liquid from the second chamber of the ultrafilter,-   step 112: verifying, while extracting liquid from the second chamber    of the ultrafilter, if the pressure in the ultrafilter second    chamber reaches a set negative pressure threshold,-   step 113: determining that the ultrafilter semipermeable membrane    has a multi-fiber break if the pressure in the second chamber during    the step of extracting liquid does not reach said set negative    pressure threshold within a set time interval. The set time interval    of said verifying step is a set time interval calculated from start    of the step of extraction of liquid from the second chamber, or    calculated from end of filling with air the first chamber of the    ultrafilter under test.

After conclusion of steps 110-113, if no multi-fiber break has beendetected the method continues with the following further steps:

-   step 114: hydraulically isolating the ultrafilter;-   step 115: waiting a given transitory period;-   step 116: verifying if two stability conditions are met, one    stability condition checking the ability to reach a certain negative    pressure, while the other condition checking the stability of    pressure.

In greater detail step 116 comprises the following sub-steps:

-   sub-step 116 a: verifying if the values of pressure in the second    chamber of the ultrafilter at the end of the transitory period are    below an auxiliary negative pressure threshold, for example below    -300 or below -350 mmHg, and-   sub-step 116 b: verifying if the variation by unit of time (dP/dt)    of the pressure values in the second chamber of the ultrafilter at    the end of the transitory period is below a set pressure    differential, for example below 4 mmHg/s.

If the verifications of sub-steps 116 a and 116 b are not bothpositively passed, the method determines that the membrane of theultrafilter has a multi-fiber break. In other words, it is sufficientthat one of the two conditions of sub-steps 116 a, 116 b not be met toconclude for the presence of a multi-fiber break.

Finally, after conclusion of steps 110-113, and in one aspect, afterconclusion also of steps 114-116, the method provides for a sequence ofsteps, namely steps 117-120) aimed at determining the possible presencein the membrane of a single fiber break. In particular, the method maycomprise the following additional steps:

-   step 118: monitoring expiration of a further test time interval    after said given transitory period;-   step 117: verifying if a variation by unit of time dP/dt of values    of pressure during the further test interval after said given    transitory period remains below a further set pressure differential;    for example it may be checked if dP/dt during the further test    interval remains below 2 mmHg/s, for at least a portion of said    further test interval, for example for 4 s in the first 10 s of the    further test interval.

Then, at step 119, it is determined that the membrane of the ultrafilterhas a single-fiber break if the above last condition is not met. If,instead, the above last condition is met, the method provides forinforming an operator or for issuing a corresponding signal to thecontroller of the apparatus 1 (step 120) .

If the above test method is applied to an ultrafilter (for example theauxiliary ultrafilter 70 of FIG. 2 ) having the first chamber connectedwith the second chamber of another already tested ultrafilter (forexample ultrafilter 19 in FIG. 2 ), the behavior of the draining pump 34(and 38) may be monitored and used to identify a multi-broken fiber inthe membrane of the first ultrafilter, causing the first chamber of theultrafilter under testing to be empty when expected to be still full ofliquid (steps 130, 131). For example, the method may include to check atime related parameter (step 130) such as the time necessary to reachP1′ or the pump rotation frequency, or the pump rotation period, andcompare this detected time related parameter with a correspondingreference threshold, assigning the identification of a multi-fiber breakproblem in the membrane of ultrafilter 19 if the check on the timerelated parameter is not passed (step 131).

Finally, according to aspects of the invention, a method of testingultrafilters may use only steps 110, 111 and 114 to 120 (without steps112-113) to identify whether an hydraulically isolated ultrafilter has asingle fiber break or a multiple fiber break, in particular by firstcreating a negative pressure in the second chamber of the ultrafilter(e.g., executing steps 110 and 111 described above) and then detectingthe behavior of derivative dp/dt to decide whether the ultrafiltermembrane is intact or has a single fiber break or multiple fiber breaks,as described above in connection with steps 116 a and 116 b and withsteps 117 and 118, and as indicated in aspects from 53rd to 81st of thesummary section.

While the invention has been described in connection with what ispresently considered to be the most practical and preferred embodiments,it is to be understood that the invention is not to be limited to thedisclosed embodiments, but on the contrary, is intended to cover variousmodifications and equivalent arrangements included within the spirit andthe scope of the appended claims.

1. A method for testing an integrity of a semipermeable membrane of anultrafilter of an extracorporeal blood treatment apparatus, theextracorporeal treatment apparatus comprising: a supply line includingan inlet end connected to a source of treatment liquid and an outlet endconnected to an inlet port of a blood treatment device, wherein theultrafilter is inserted in the supply line and the semipermeablemembrane divides the ultrafilter into a first chamber and a secondchamber, the ultrafilter including a first port connecting a first tractof the supply line to the first chamber, and a second port connectingthe second chamber to a second tract of the supply line; a waste lineincluding an inlet end connected to an outlet port of the bloodtreatment device and an outlet end connected to a discharge of usedtreatment liquid; an air inlet line connected to the first chamber ofthe ultrafilter or to the first tract of the supply line; at least onewaste pump located on the waste line; and at least one pressure sensorconfigured to detect a pressure in one of: the second chamber of theultrafilter, the second tract of the supply line, or the waste line,wherein the method comprises: filling the first chamber of theultrafilter with air through the air inlet line, verifying when, whilethe waste pump is running, the pressure sensed by the at least onepressure sensor reaches a set negative pressure threshold (Pt), anddetermining that the ultrafilter semipermeable membrane has amulti-fiber break when the sensed pressure does not reach the setnegative pressure threshold (Pt) within a set time interval (T), thepressure being considered relative to atmospheric pressure present in alocation where the extracorporeal blood treatment apparatus operates. 2.The method of claim 1 wherein, after filling the first chamber with air,the waste pump is operated to make pressure in the second chamber morenegative or to create a negative pressure in the second chamber.
 3. Themethod according to claim 1, wherein verifying the measured pressuredoes not reach the set negative pressure threshold (Pt) comprisesdetecting pressure by the pressure sensor after expiration of the settime interval (T).
 4. The method according to claim 1, wherein verifyingthe measured pressure does not reach the set negative pressure threshold(Pt) comprises detecting pressure by the pressure sensor and measuringan actual time interval at which the negative pressure threshold (Pt) isreached.
 5. The method according to claim 1, wherein filling the firstchamber with air comprises opening an air valve or operating an air pumplocated on the air inlet line.
 6. The method according to claim 1,wherein operating the waste pump causes extracting or continuing toextract liquid from the second chamber of the ultrafilter, and whereinoperating the waste pump after filling the first chamber with air makespressure in the second chamber more negative or creates a negativepressure in the second chamber.
 7. A method for testing an integrity ofa semipermeable membrane of an ultrafilter, wherein the semipermeablemembrane separates the ultrafilter into a first and a second chamber,the method comprising: emptying the first chamber of the ultrafilterfrom liquid and filling the first chamber with air; after the firstchamber has been filled with air, extracting or continuing to extractliquid from the second chamber of the ultrafilter; verifying, whileextracting liquid from the second chamber of the ultrafilter, when thepressure in the second chamber of the ultrafilter reaches a set negativepressure threshold (Pt); determining that the semipermeable membrane hasa multi-fiber break when the pressure in the second chamber during thestep of extracting liquid does not reach the set negative pressurethreshold (Pt) within a set time interval (T), wherein the pressure inthe second chamber is considered relative to atmospheric pressurepresent in a location where the ultrafilter operates.
 8. The methodaccording to claim 7, wherein verifying the measured pressure does notreach the set negative pressure threshold (Pt) comprises detecting thepressure in one of: the second chamber of the ultrafilter, or a lineconnected to the second chamber of the ultrafilter, after expiration ofthe set time interval (T).
 9. The method according to claim 7, whereinverifying the measured pressure does not reach the set negative pressurethreshold (Pt) comprises detecting the pressure in one of: the secondchamber of the ultrafilter, and a line connected to the second chamberof the ultrafilter; and measuring an actual time interval at which thenegative pressure threshold (Pt) is reached.
 10. The method according toclaim 7, wherein an air inlet line is connected to the first chamber ofthe ultrafilter, and wherein the steps of emptying the first chamber ofthe ultrafilter from liquid and filling the first chamber with aircomprise opening an air valve or operating an air pump located on theair inlet line.
 11. The method according to claim 7, wherein extractingor continuing to extract liquid from the second chamber of theultrafilter after filling the first chamber with air makes pressure inthe second chamber more negative or creates a negative pressure in thesecond chamber.
 12. The method according to claim 7, wherein: theultrafilter is inserted in a supply line including an inlet endconnected to a source of treatment liquid and an outlet end connected toan inlet port of a blood treatment device, the ultrafilter having afirst port connecting a first tract of the supply line to the firstchamber of the same ultrafilter, and a second port connecting the secondchamber of the ultrafilter to a second tract of the supply line; a wasteline including an inlet end is connected to an outlet port of the bloodtreatment device and an outlet end is connected to a discharge of usedtreatment liquid; a waste pump is positioned on the waste line; and anair inlet line is connected to the first chamber of the ultrafilter orto the first tract of the supply line, wherein said step of extractingliquid from the second chamber is achieved by operating the waste pump,and wherein said step of verifying takes place while the waste pump isrunning.
 13. A method for testing an integrity of a semipermeablemembrane of an ultrafilter of an extracorporeal blood treatmentapparatus, the extracorporeal treatment apparatus comprising: a supplyline including an inlet end connected to a source of treatment liquidand an outlet end connected to an inlet port of a blood treatmentdevice, wherein the ultrafilter is inserted in the supply line and thesemipermeable membrane divides the ultrafilter into a first chamber anda second chamber, the ultrafilter including a first port connecting afirst tract of the supply line to the first chamber, and a second portconnecting the second chamber to a second tract of the supply line; awaste line including an inlet end connected to an outlet port of theblood treatment device and an outlet end connected to a discharge ofused treatment liquid; and a waste pump located on the waste line, themethod comprising the following steps: emptying the first chamber of theultrafilter from liquid and filling the first chamber with air,operating the waste pump to extract or to continue extracting liquidfrom the second chamber of the ultrafilter, verifying, while the wastepump is operating, when the pressure in the second chamber of theultrafilter reaches a set negative pressure threshold (Pt), anddetermining that the semipermeable membrane has a fiber break when,while operating the waste pump, the pressure in the second chamber doesnot reach the set negative pressure threshold (Pt) within a set timeinterval (T), the pressure being considered relative to atmosphericpressure present in a location where the extracorporeal blood treatmentapparatus operates.
 14. The method according to claim 13, whereinverifying the measured pressure does not reach the set negative pressurethreshold (Pt) comprises detecting the pressure in one of: the secondchamber of the ultrafilter, or a line connected to the second chamber ofthe ultrafilter, after expiration of the set time interval (T).
 15. Themethod according to claim 13, wherein verifying the measured pressuredoes not reach the set negative pressure threshold (Pt) comprisesdetecting pressure in one of: the second chamber of the ultrafilter, ora line connected to the second chamber of the ultrafilter; and andmeasuring an actual time interval at which the negative pressurethreshold (Pt) is reached.
 16. The method according to claim 13, whereinan air inlet line is connected to the first chamber of the ultrafilter,and wherein the steps of emptying the first chamber of the ultrafilterfrom liquid and filling the first chamber with air comprise opening anair valve or operating an air pump located on the air inlet line. 17.The method according to claim 13, wherein operating the waste pump toextract or to continue extracting liquid from the second chamber of theultrafilter takes place until after the first chamber has been filledwith air.
 18. The method according to claim 17, wherein operating thewaste pump after filling the first chamber with air makes pressure inthe second chamber more negative or creates a negative pressure in thesecond chamber.
 19. The method according to claim 16, wherein the methodfurther includes: while filling the first chamber of the ultrafilterwith air, operating the waste pump based on a first set negativepressure value (P1), which is a desired set value to be reached by thepressure sensed by the at least one pressure sensor; and after the stepof filling the first chamber of the ultrafilter with air, once the firstchamber has been emptied from liquid and filled with air, operating thewaste pump based on a second set negative pressure value (P2), which isa desired set value to be reached by the pressure sensed by the at leastone pressure sensor and which is more negative than the first pressurevalue, wherein the set negative pressure threshold (Pt), which ischecked during the verifying step, has a negative value intermediatebetween the first set pressure value (P1) and the second set pressurevalue (P2).
 20. The method according to claim 19, wherein: the first setpressure value (P1) is selected in a pressure range between -150 mmHgand -450 mmHg; and the second set pressure value (P2) is selected in apressure range between -300 mmHg and -700 mmHg, with the condition thatthe second pressure value be at least 100 mmHg more negative than thefirst set pressure value.